999 Ann Rheum Dis: first published as 10.1136/ard.62.10.999 on 12 September 2003. Downloaded from CONCISE REPORT Renal artery stenosis in the antiphospholipid (Hughes) syndrome and hypertension S R Sangle, D P D’Cruz, W Jan, M Y Karim, M A Khamashta, I C Abbs,GRVHughes ............................................................................................................................. Ann Rheum Dis 2003;62:999–1002 11 with primary APS, and 6 with aPL only) and uncontrolled Background: Hypertension is common in the anti- hypertension. All patients had attended the St Thomas’ phospholipid (Hughes) syndrome (APS) and its cause is Hospital Lupus Unit over the previous five years. Patients with poorly understood. Anecdotal evidence suggests that renal SLE were classified by the American College of Rheumatology artery stenosis (RAS) may be a relevant and treatable classification criteria for SLE.7 Patients with APS had a history cause of hypertension. of thrombosis or pregnancy morbidity, or both, in addition to Objective: To investigate the prevalence of RAS in positive aPL on two separate occasions at least six weeks apart, patients with APS and hypertension. as defined by the preliminary classification criteria established Patients and methods: Three groups of patients were in Sapporo.8 Six patients had only positive aPL antibodies. evaluated: (1) 77 patients with positive antiphospholipid Group 2: 91 hypertensive patients attended the hypertension antibodies (aPL) (60 secondary APS, 11 primary APS, and and renal clinics in St Thomas’ and Guy’s Hospital and were 6 with aPL only) and uncontrolled hypertension who were investigated for their uncontrolled hypertension. receiving two or more antihypertensive drugs; (2) 91 patients (<50 years) attending hypertension clinics;(3) 92 Group 3: 92 healthy, normotensive, aPL antibody negative normotensive healthy, potential renal transplant donors. patients, who were assessed before considering donation of a Magnetic resonance renal angiography was used to kidney for transplantation. image the renal arteries in all three groups. Patients in group 1 were assessed prospectively and groups Results: Group 1: 20/77 (26%) patients had evidence of 2 and 3 were assessed in the previous three years. RAS (16 unilateral and 4 bilateral). Sixteen patients (80%) Blood pressure was measured at every clinic visit (three had smooth well defined stenoses in the proximal third of months) in groups 1 and 2. All patients with APS had had the renal artery. Three further patients had irregular arter- repeated blood pressure measurements >150/100 mm Hg ies without distinct stenosis. Group 2: 7/91 (8%) hyperten- despite receiving two or more antihypertensive agents. sive patients had RAS (χ2=10.3, p<0.001 v group 1). Magnetic resonance imaging angiography (MRA) was used Group 3: 3/92 (3%) healthy donors had RAS (χ2=18.2, non-invasively to image the renal arteries in the St Thomas’ p<0.0001 v group 1). Hospital radiology department. A bolus of contrast medium Conclusion: A significantly increased prevalence of RAS gadolinium 0.3 ml/kg body weight was injected into the http://ard.bmj.com/ (26%) was found in patients with APS and hypertension, antecubital vein. The image acquisition was performed after compared with relatively young (<50 years) hypertensive visualisation of the aorta and its renal branches using the controls and healthy potential donors. bolus track. T1 and T2 weighted images were processed with maximum intensity projection construction by an experienced radiologist at a workstation. MRA (73 patients) was used to study the renal arteries, two patients had contrast computed n 1934 Goldblatt and Lynch demonstrated that hyper- tomography (CT) angiography, and two underwent intra- tension could be produced in dogs by constricting both renal venous contrast angiography, as MRA was not possible. In on September 28, 2021 by guest. Protected copyright. Iarteries or removal of one kidney.1 In 1938 Houssay and groups 2 and 3, all patients had MRA of the renal arteries Taqueni provided evidence for the role of renin in the develop- using the same protocol. ment of hypertension in the ischaemic kidney.2 Since then extensive clinical experience has linked renal artery stenosis Baseline clinical parameters (RAS) or occlusion with hypertension. Recently a “new” and Group 1 comprised 65 women and 12 men with a median age possibly major cause of renovascular hypertension—the anti- of 45 years (range 19–72). The racial distribution included 61 phospholipid syndrome (APS, Hughes syndrome), has been white, 9 black, and 7 patients of Asian origin. The median added to the list.3–6 Hypertension was noted in the original duration of disease was 16 years (range 4–23). The median µ descriptions of APS, and was thought to be secondary to reno- creatinine concentration was 184 mol/l. Eleven patients were vascular changes.3 We considered that renal artery occlusion, diabetic and 10 hyperlipidaemic, for which they were receiving as in other arteries, might be a feature of APS.3 In 2000 we lipid lowering agents. The mean systolic blood pressure of all published an account of a small series of patients with RAS in the patients was 160 mm Hg and diastolic 100 mm Hg. Three patients with APS associated with hypertension.6 We consid- patients were overweight (body mass index (BMI) >28) and ered it important, therefore, to establish the prevalence of RAS 11 were chronic smokers (table 1) These results refer to the in a group of patients with APS with uncontrolled hyper- whole of group 1 not just the patients with RAS. tension. Ethical approval was obtained for this preliminary study from the St Thomas’ Hospital ethics committee. ............................................................. PATIENTS AND METHODS Abbreviations: aCL, anticardiolipin antibodies; aPL, antiphospholipid We evaluated three groups: antibodies; APS, antiphospholipid syndrome; BMI, body mass index; CT, computed tomography; INR, international normalised ratio; MRA, Group 1: 77 patients with positive antiphospholipid antibodies magnetic resonance imaging angiography; ox-LDL, oxidised low density (aPL) (60 with systemic lupus erythematosus (SLE) and APS, lipoprotein; RAS, renal artery stenosis; SLE, systemic lupus erythematosus www.annrheumdis.com 1000 Sangle, D’Cruz, Jan, et al Ann Rheum Dis: first published as 10.1136/ard.62.10.999 on 12 September 2003. Downloaded from Table 1 Baseline parameters of patients with APS and hypertension Patients with no Patients with Patients (n=77) RAS (n=57) RAS (n=20) Primary APS 9 4 Secondary APS 48 16 Median age (years) 45 43 Mean systolic BP (mm Hg) 160 155 Mean diastolic BP (mm Hg) 100 104 Median creatinine (µmol/l) 184 185 Diabetes 11 2 Smoking 10 1 Steroids (prednisolone) 26 10 Hyperlipidaemia 10 2 Obesity/overweight 2 1 Nephritic/nephrotic syndrome 11 2 Past thrombotic events 55 18 (arterial/venous) Pregnancy related morbidity 41 4 Figure 1 Magnetic resonance angiography showing renal artery APS, antiphospholipid syndrome; RAS, renal artery stenosis. stenosis in a patient with APS and hypertension. All except 12 patients had had other arterial/venous throm- botic episodes such as cerebrovascular accident, deep venous thrombosis, pulmonary embolism, ischaemic heart disease, and gangrene. Forty two patients had pregnancy related com- plications. Six patients were positive for aPL only, without any vascular occlusions or pregnancy related morbidity. In group 2, 91 hypertensive (≤50 years) patients were investigated for their uncontrolled hypertension. Their mean age was 42 years (18–50) and 46 were female. Group 3 consisted of 92 healthy subjects, who were investigated as prospective kidney donors. Their mean age was 52 years (22– 59). Statistical analysis Categorical data were assessed non-parametrically with the χ2 test with Yates’s correction for small numbers where appropriate. RESULTS Imaging of renal arteries Figure 2 RAS confirmed on arteriography. The lesion is a long http://ard.bmj.com/ Examination of the renal arteries in group 1 (77 patients) smooth stenosis with no evidence of atheroma. showed RAS in 20 patients (26%). In 16 the lesions were uni- lateral, while four had bilateral RAS. Sixteen patients had respectively. Two were diabetic and two had hypercholesterol- smooth well delineated stenoses situated in the proximal one aemia. Their median age was 43 years (19 –62). One patient third of the artery from the ostium (figs 1 and 2). In these 16 had had dissection of the descending aorta. One of these patients, the aorta above and below the renal arteries was patients was obese and all were Caucasian in origin. Eighteen uniformly smooth and regular. The remaining four had of these patients had had venous or arterial thrombotic events. on September 28, 2021 by guest. Protected copyright. irregular, tortuous renal arteries and aorta, suggesting athero- Four patients had pregnancy related morbidity. sclerotic lesions. Three further patients had irregular renal arteries, without evidence of distinct stenosis. Fifteen of the 20 Therapy patients had secondary APS and three had primary APS. Two All but two patients with RAS were treated with anticoagu- patients with RAS were aPL positive only. In group 2 of young lants (recommended international normalised ratio (INR) hypertensive patients, 7/91 (8%) patients had RAS and in five 3.0–4.0). the appearance was suggestive of fibromuscular dysplasia. In The indication for anticoagulation in 14 patients was recur- group 3, only 3/92 (3%) subjects had RAS. The prevalence of rent arterial/or venous thrombosis. Four patients were anti- RAS was significantly higher in group 1 than in both control coagulated as it was thought that RAS as a potential groups (χ2=10.3, p=0.001 v group 2 and χ2 =18.2, p<0.0001 v thrombotic event might compromise renal function. group 3). Patients with APS with RAS Progress of patients Renal parameters MRA/CT contrast angiography was repeated in five patients In the patients with APS, the median creatinine level was 185 for suspected re-stenosis (renal bruit 3, impaired renal µmol/l (range 64–350).